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Keywords: Hemophilia A, Factor VIII, Hemorrhage, Coagulation factor VIII Introduction Hereditary deficiency of each coagulation factor in hemostatic cascade is explained. Hemophilia A (HA) is the most common coagulation factor deficiency around the world with high treatment cost.1 It affects all ethnic populations2 and its prevalence varies among different countries, but estimated TRIB1 at a rate of 3-20 cases per 100,000 population.3-5 The World Federation of Hemophilia (WFH) has estimated the total number of hemophilia at about 500,000 universally, while one-third are diagnosed.6 About 30-33% of the new diagnosed cases of the current X-linked disorder show no family history; reflecting on its occurrence by spontaneous or sporadic mutations.1,7,8 Genetically, it stems from the deletion of the whole or part of gene, point mutations gene or in regulators of the gene,9 and major inversion of the tip of X-chromosome that is responsible for 50% of the severe form.10 Such variety of abnormalities in factor VIII gene result in the absence of impaired molecule production of factor VIII, which has no function or reduction of factor VIII in the plasma of the affected individuals and cause a tendency to bleed with Ibrutinib research buy various severities that correlate with the plasma level of factor VIII. HA or classical hemophilia accounts for about 80% of all hemophiliacs. This lifelong disorder has three phenotypes (severe, moderate and mild) that correlates with factor VIII (FVIII) levels in plasma (mTOR inhibitor therapeutic facilities, the median life expectancy has been increased noticeably.15 The purpose of the current review was to collect and summarize publications to present the state-of-the-art on clinical manifestations of hemophilia A and laboratory approaches in diagnosing the undiagnosed individuals with bleeding and suspect to hemophilia A. Clinical Manifestations The classification of HA provides a guidance to possible types of bleeding and the rate of occurrence of hemorrhagic episodes. The patients with severe form, experience spontaneous bleeding and hemorrhage after minor trauma about 1-6 times in a month, including hemarthrosis and intramuscular hemorrhage. In moderate form, the affected patients usually experience bleeding after mild to moderate injuries, while HA patients with mild form may not be diagnosed for years and bleed after surgery or major trauma.